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Volume 31, Issue 8
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Alzheimer's disease (AD) remains one of the hardest neurodegenerative diseases to treat due to its enduring cognitive deterioration and memory loss. Despite extensive research, few viable treatment approaches have been found; these are mostly due to several barriers, such as the disease's complex biology, limited pharmaceutical efficacy, and the BBB. This presentation discusses current strategies for addressing these therapeutic barriers to enhance AD treatment. Innovative drug delivery methods including liposomes, exosomes, and nanoparticles may be able to pass the blood-brain barrier and allow medicine to enter specific brain regions. These innovative strategies of medicine distribution reduce systemic side effects by improving absorption. Moreover, the development of disease-modifying treatments that target tau protein tangles, amyloid-beta plaques, and neuroinflammation offers the chance to influence the course of the illness rather than only treat its symptoms. Furthermore, gene therapy and CRISPR-Cas9 technologies have surfaced as potentially ground-breaking methods for addressing the underlying genetic defects associated with AD. Furthermore, novel approaches to patient care may involve the utilization of existing medications having neuroprotective properties, such as those for diabetes and cardiovascular conditions. Furthermore, biomarker research and personalized medicine have made individualized therapy approaches possible, ensuring that patients receive the best care possible based on their unique genetic and molecular profiles.

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2025-05-31

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References

  1. ChitramuthuBP. BennettHP. BatemanA. History of neurodegenerative diseases and its impact on aged population in India: An assessment.Indian J. Sci.2017521106115
     [Google Scholar]
  2. Parra-DamasA. SauraC.A. Tissue clearing and expansion methods for imaging brain pathology in neurodegeneration: From circuits to synapses and beyond.Front. Neurosci.20201491410.3389/fnins.2020.0091433122983
     [Google Scholar]
  3. ZvěřováM. Clinical aspects of Alzheimer’s disease.Clin. Biochem.2019723610.1016/j.clinbiochem.2019.04.01531034802
     [Google Scholar]
  4. MandellA.M. GreenR.C. Alzheimer’s disease.The Handbook of Alzheimer’s Disease and other Dementias.Wiley Blackwell2014391
     [Google Scholar]
  5. MendezM.F. Early-onset Alzheimer disease.Neurol. Clin.201735226328110.1016/j.ncl.2017.01.00528410659
     [Google Scholar]
  6. ZetterbergH. MattssonN. Understanding the cause of sporadic Alzheimer’s disease.Expert Rev. Neurother.201414662110.1586/14737175.2014.91574024852227
     [Google Scholar]
  7. RaphaelD de L. The knowledge and attitudes of primary care and the barriers to early detection and diagnosis of Alzheimer’s disease.Med (N. Y.)2022587906
     [Google Scholar]
  8. ZucchellaC. SinforianiE. TamburinS. FedericoA. MantovaniE. BerniniS. CasaleR. BartoloM. The multidisciplinary approach to Alzheimer’s disease and dementia. A narrative review of non-pharmacological treatment.Front. Neurol.20189105810.3389/fneur.2018.0105830619031
     [Google Scholar]
  9. DavisK.D. AghaeepourN. AhnA.H. AngstM.S. BorsookD. BrentonA. BurczynskiM.E. CreanC. EdwardsR. GaudilliereB. HergenroederG.W. IadarolaM.J. IyengarS. JiangY. KongJ.T. MackeyS. SaabC.Y. SangC.N. ScholzJ. SegerdahlM. TraceyI. VeasleyC. WangJ. WagerT.D. WasanA.D. PelleymounterM.A. Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: Challenges and opportunities.Nat. Rev. Neurol.202016738140010.1038/s41582‑020‑0362‑232541893
     [Google Scholar]
  10. DebA. ThorntonJ.D. SambamoorthiU. InnesK. Direct and indirect cost of managing Alzheimer’s disease and related dementias in the United States.Expert Rev. Pharmacoecon. Outcomes Res.201717218920210.1080/14737167.2017.131311828351177
     [Google Scholar]
  11. GrillJ.D. KarlawishJ. Addressing the challenges to successful recruitment and retention in Alzheimer’s disease clinical trials.Alzheimers Res. Ther.2010263410.1186/alzrt5821172069
     [Google Scholar]
  12. JichaG.A. CarrS.A. Conceptual evolution in Alzheimer’s disease: Implications for understanding the clinical phenotype of progressive neurodegenerative disease.J. Alzheimers Dis.201019125327210.3233/JAD‑2010‑123720061643
     [Google Scholar]
  13. BrawleyE.C. Designing for Alzheimer’s disease. Strategies for creating better care environments. (1st ed.) New York: Wiley 1997; p. 295.
  14. DeKoskyS.T. Epidemiology and pathophysiology of Alzheimer’s disease.Clin. Cornerstone200134152610.1016/S1098‑3597(01)90045‑611432119
     [Google Scholar]
  15. AshrafianH. ZadehE.H. KhanR.H. Review on Alzheimer’s disease: Inhibition of amyloid beta and tau tangle formation.Int. J. Biol. Macromol.202116738239410.1016/j.ijbiomac.2020.11.19233278431
     [Google Scholar]
  16. TakahashiR.H. NagaoT. GourasG.K. Plaque formation and the intraneuronal accumulation of β-amyloid in Alzheimer’s disease.Pathol. Int.201767418519310.1111/pin.1252028261941
     [Google Scholar]
  17. WangW.Y. TanM.S. YuJ.T. TanL. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease.Ann. Transl. Med.201531013626207229
     [Google Scholar]
  18. ZhangF. JiangL. Neuroinflammation in Alzheimer's disease.Neuropsychiatr. Dis. Treat.2015243Jan
     [Google Scholar]
  19. CarlsonN.G. WieggelW.A. ChenJ. BacchiA. RogersS.W. GahringL.C. Inflammatory cytokines IL-1 α, IL-1 β, IL-6, and TNF-α impart neuroprotection to an excitotoxin through distinct pathways.J. Immunol.199916373963396810.4049/jimmunol.163.7.396310490998
     [Google Scholar]
  20. González-ReyesR.E. Nava-MesaM.O. Vargas-SánchezK. Ariza-SalamancaD. Mora-MuñozL. Involvement of astrocytes in Alzheimer’s disease from a neuroinflammatory and oxidative stress perspective.Front. Mol. Neurosci.20171042710.3389/fnmol.2017.0042729311817
     [Google Scholar]
  21. CriminsJ.L. PoolerA. PolydoroM. LuebkeJ.I. Spires-JonesT.L. The intersection of amyloid β and tau in glutamatergic synaptic dysfunction and collapse in Alzheimer’s disease.Ageing Res. Rev.201312375776310.1016/j.arr.2013.03.00223528367
     [Google Scholar]
  22. SchliebsR. ArendtT. The cholinergic system in aging and neuronal degeneration.Behav. Brain Res.2011221255556310.1016/j.bbr.2010.11.05821145918
     [Google Scholar]
  23. LaurentC. BuéeL. BlumD. Tau and neuroinflammation: What impact for Alzheimer’s disease and tauopathies?Biomed. J.2018411213310.1016/j.bj.2018.01.00329673549
     [Google Scholar]
  24. JohnA. ReddyP.H. Synaptic basis of Alzheimer’s disease: Focus on synaptic amyloid beta, P-tau and mitochondria.Ageing Res. Rev.20216510120810.1016/j.arr.2020.10120833157321
     [Google Scholar]
  25. Chartier-HarilnM-C. ParfittM. LegrainS. Pérez-TurJ. BrousseauT. EvansA. BerrC. VldalO. RoquesP. GourletV. FruchartJ-C. DelacourteA. RossorM. AmouyelP. Apolipoprotein E, ɛ4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer’s disease: Analysis of the 19q13.2 chromosomal region.Hum. Mol. Genet.19943456957410.1093/hmg/3.4.5698069300
     [Google Scholar]
  26. WisemanF.K. PulfordL.J. BarkusC. LiaoF. PorteliusE. WebbR. Chávez-GutiérrezL. CleverleyK. NoyS. SheppardO. CollinsT. PowellC. SarellC.J. RickmanM. ChoongX. ToshJ.L. SiganporiaC. WhittakerH.T. StewartF. SzarugaM. MurphyM.P. BlennowK. de StrooperB. ZetterbergH. BannermanD. HoltzmanD.M. TybulewiczV.L.J. FisherE.M.C. StrydomA. FisherE. NizeticD. HardyJ. TybulewiczV. Karmiloff-SmithA. London Down syndrome consortium LonDownS Consortium Trisomy of human chromosome 21 enhances amyloid-β deposition independently of an extra copy of APP.Brain201814182457247410.1093/brain/awy15929945247
     [Google Scholar]
  27. UddinM.S. KabirM.T. BegumM.M. IslamM.S. BehlT. AshrafG.M. Retracted article: Exploring the role of clu in the pathogenesis of Alzheimer’s disease.Neurotox. Res.20213962108211910.1007/s12640‑020‑00271‑432820456
     [Google Scholar]
  28. RosenthalS.L. KambohM.I. Late-onset Alzheimer’s disease genes and the potentially implicated pathways.Curr. Genet. Med. Rep.2014228510110.1007/s40142‑014‑0034‑x24829845
     [Google Scholar]
  29. ArmstrongR. Risk factors for Alzheimer’s disease.Folia Neuropathol.20195728710510.5114/fn.2019.8592931556570
     [Google Scholar]
  30. GrossbergG.T. Cholinesterase inhibitors for the treatment of Alzheimer’s disease: Getting on and staying on.Curr. Ther. Res. Clin. Exp.200364421623510.1016/S0011‑393X(03)00059‑624944370
     [Google Scholar]
  31. HaakeA. NguyenK. FriedmanL. ChakkamparambilB. GrossbergG.T. An update on the utility and safety of cholinesterase inhibitors for the treatment of Alzheimer’s disease.Expert Opin. Drug Saf.202019214715710.1080/14740338.2020.172145631976781
     [Google Scholar]
  32. LiuJ. ChangL. SongY. LiH. WuY. The role of NMDA receptors in Alzheimer’s disease.Front. Neurosci.201913FEB4310.3389/fnins.2019.0004330800052
     [Google Scholar]
  33. ChenJ. DuanY. LiH. LuL. LiuJ. TangC. Different durations of cognitive stimulation therapy for Alzheimer’s disease: A systematic review and meta-analysis.Clin. Interv. Aging2019141243125410.2147/CIA.S21006231371930
     [Google Scholar]
  34. GilbertA.G. Creative dance for all ages. (2nd ed). Creat Danc All Ages 2015; pp.1-376.10.5040/9781718212763
  35. BhattiG.K. ReddyA.P. ReddyP.H. BhattiJ.S. Lifestyle modifications and nutritional interventions in aging-associated cognitive decline and Alzheimer’s disease.Front. Aging Neurosci.20201136910.3389/fnagi.2019.0036931998117
     [Google Scholar]
  36. SteffenL.M. JacobsD.R.Jr StevensJ. ShaharE. CarithersT. FolsomA.R. Associations of whole-grain, refined-grain, and fruit and vegetable consumption with risks of all-cause mortality and incident coronary artery disease and ischemic stroke: The Atherosclerosis Risk in Communities (ARIC) study.Am. J. Clin. Nutr.200378338339010.1093/ajcn/78.3.38312936919
     [Google Scholar]
  37. AlissaE.M. FernsG.A. Dietary fruits and vegetables and cardiovascular diseases risk.Crit. Rev. Food Sci. Nutr.20175791950196226192884
     [Google Scholar]
  38. ViswanathanM. GolinC.E. JonesC.D. AshokM. BlalockS.J. WinesR.C.M. Coker-SchwimmerE.J.L. RosenD.L. SistaP. LohrK.N. Interventions to improve adherence to self-administered medications for chronic diseases in the United States: A systematic review.Ann. Intern. Med.20121571178579510.7326/0003‑4819‑157‑11‑201212040‑0053822964778
     [Google Scholar]
  39. BurnierM. EganB.M. Adherence in hypertension.Circ. Res.201912471124114010.1161/CIRCRESAHA.118.31322030920917
     [Google Scholar]
  40. IqbalI. SaqibF. MubarakZ. LatifM.F. WahidM. NasirB. ShahzadH. Sharifi-RadJ. MubarakM.S. Alzheimer’s disease and drug delivery across the blood-brain barrier: Approaches and challenges.Eur. J. Med. Res.202429131310.1186/s40001‑024‑01915‑338849950
     [Google Scholar]
  41. FillitHM O’ConnellAW BrownWM Barriers to drug discovery and development for Alzheimer disease.Alzheimer Dis Assoc Disord20021611810.1097/00002093‑200200001‑00001
     [Google Scholar]
  42. ZhouM. FuX. MaB. ChenZ. ChengY. LiuL. KanS. ZhaoX. FengS. JiangZ. ZhuR. Effects of low-intensity ultrasound opening the blood-brain barrier on Alzheimer’s disease-a mini review.Front. Neurol.202314127464210.3389/fneur.2023.127464238020620
     [Google Scholar]
  43. DeoA.K. BorsonS. LinkJ.M. DominoK. EaryJ.F. KeB. RichardsT.L. MankoffD.A. MinoshimaS. O’SullivanF. EyalS. HsiaoP. MaravillaK. UnadkatJ.D. Activity of P-glycoprotein, a β-amyloid transporter at the blood-brain barrier, is compromised in patients with mild Alzheimer disease.J. Nucl. Med.20145571106111110.2967/jnumed.113.13016124842892
     [Google Scholar]
  44. EwersM. MielkeM.M. HampelH. Blood-based biomarkers of microvascular pathology in Alzheimer’s disease.Exp. Gerontol.2010451757910.1016/j.exger.2009.09.00519782124
     [Google Scholar]
  45. TsartsalisS. SlevenH. FancyN. WesselyF. SmithA.M. WillumsenN. CheungT.K.D. RokickiM.J. ChauV. IfieE. KhozoieC. AnsorgeO. YangX. JenkynsM.H. DaveyK. McGarryA. MuirheadR.C.J. DebetteS. JacksonJ.S. MontagneA. OwenD.R. MinersJ.S. LoveS. WebberC. CaderM.Z. MatthewsP.M. A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer’s disease.Nat. Commun.2024151224310.1038/s41467‑024‑46630‑z38472200
     [Google Scholar]
  46. SweeneyM.D. MontagneA. SagareA.P. NationD.A. SchneiderL.S. ChuiH.C. HarringtonM.G. PaJ. LawM. WangD.J.J. JacobsR.E. DoubalF.N. RamirezJ. BlackS.E. NedergaardM. BenvenisteH. DichgansM. IadecolaC. LoveS. BathP.M. MarkusH.S. Al-Shahi SalmanR. AllanS.M. QuinnT.J. KalariaR.N. WerringD.J. CarareR.O. TouyzR.M. WilliamsS.C.R. MoskowitzM.A. KatusicZ.S. LutzS.E. LazarovO. MinshallR.D. RehmanJ. DavisT.P. WellingtonC.L. GonzálezH.M. YuanC. LockhartS.N. HughesT.M. ChenC.L.H. SachdevP. O’BrienJ.T. SkoogI. PantoniL. GustafsonD.R. BiesselsG.J. WallinA. SmithE.E. MokV. WongA. PassmoreP. BarkofF. MullerM. BretelerM.M.B. RománG.C. HamelE. SeshadriS. GottesmanR.F. van BuchemM.A. ArvanitakisZ. SchneiderJ.A. DrewesL.R. HachinskiV. FinchC.E. TogaA.W. WardlawJ.M. ZlokovicB.V. Vascular dysfunction-The disregarded partner of Alzheimer’s disease.Alzheimers Dement.201915115816710.1016/j.jalz.2018.07.22230642436
     [Google Scholar]
  47. KelleherR.J. SoizaR.L. Evidence of endothelial dysfunction in the development of Alzheimer’s disease: Is Alzheimer’s a vascular disorder?Am. J. Cardiovasc. Dis.20133419722624224133
     [Google Scholar]
  48. AbbottN.J. RönnbäckL. HanssonE. Astrocyte-endothelial interactions at the blood-brain barrier.Nat. Rev. Neurosci.200671415310.1038/nrn182416371949
     [Google Scholar]
  49. PardridgeW.M. Treatment of Alzheimer’s disease and blood-brain barrier drug delivery.Pharmaceuticals2020131139410.3390/ph1311039433207605
     [Google Scholar]
  50. Dufaÿ WojcickiA. HillaireauH. NascimentoT.L. ArpiccoS. TavernaM. RibesS. BourgeM. NicolasV. BochotA. VauthierC. TsapisN. FattalE. Hyaluronic acid-bearing lipoplexes: Physico-chemical characterization and in vitro targeting of the CD44 receptor.J. Control. Release2012162354555210.1016/j.jconrel.2012.07.01522820451
     [Google Scholar]
  51. BallabhP. BraunA. NedergaardM. The blood-brain barrier: An overview.Neurobiol. Dis.200416111310.1016/j.nbd.2003.12.01615207256
     [Google Scholar]
  52. SaraivaC. PraçaC. FerreiraR. SantosT. FerreiraL. BernardinoL. Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.J. Control. Release2016235344710.1016/j.jconrel.2016.05.04427208862
     [Google Scholar]
  53. Fonseca-SantosB. ChorilliM. Palmira Daflon GremiãoM. Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease.Int. J. Nanomedicine201510Aug4981500310.2147/IJN.S8714826345528
     [Google Scholar]
  54. AtriA. Effective pharmacological management of Alzheimer’s disease. Am J Manag Care20111713345355
     [Google Scholar]
  55. FonsecaL.C. LopesJ.A. VieiraJ. ViegasC. OliveiraC.S. HartmannR.P. FonteP. Intranasal drug delivery for treatment of Alzheimer’s disease.Drug Deliv. Transl. Res.202111241142510.1007/s13346‑021‑00940‑733638130
     [Google Scholar]
  56. JacksonS. HamR.J. WilkinsonD. The safety and tolerability of donepezil in patients with Alzheimer’s disease.Br. J. Clin. Pharmacol.200458s1Suppl. 11810.1111/j.1365‑2125.2004.01848.x15496217
     [Google Scholar]
  57. BirksJS Cochrane Dementia and Cognitive Improvement Group Cholinesterase inhibitors for Alzheimer’s disease.Cochrane Database Syst Rev2006 20061CD00559310.1002/14651858.CD005593
     [Google Scholar]
  58. PrvulovicD. HampelH. PantelJ. Galantamine for Alzheimer’s disease.Expert Opin. Drug Metab. Toxicol.20106334535410.1517/1742525100359213720113148
     [Google Scholar]
  59. ParsonsC.G. DanyszW. QuackG. Memantine is a clinically well tolerated N-methyl-d-aspartate (NMDA) receptor antagonist-a review of preclinical data.Neuropharmacology199938673576710.1016/S0028‑3908(99)00019‑210465680
     [Google Scholar]
  60. TariotP.N. FarlowM.R. GrossbergG.T. GrahamS.M. McDonaldS. GergelI. for the Memantine Study Group Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: A randomized controlled trial.JAMA2004291331732410.1001/jama.291.3.31714734594
     [Google Scholar]
  61. SallowayS. ChalkiasS. BarkhofF. BurkettP. BarakosJ. PurcellD. SuhyJ. ForrestalF. TianY. UmansK. WangG. SinghalP. Budd HaeberleinS. SmirnakisK. Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early Alzheimer disease.JAMA Neurol.2022791132110.1001/jamaneurol.2021.416134807243
     [Google Scholar]
  62. SteckA. Lecanemab in early Alzheimer’s disease.N Engl J Med20233881921
     [Google Scholar]
  63. SmallG. DuboisB. A review of compliance to treatment in Alzheimer’s disease: Potential benefits of a transdermal patch.Curr. Med. Res. Opin.200723112705271310.1185/030079907X23340317892635
     [Google Scholar]
  64. ScialliA.R. SaavedraK. Fugh-BermanA. The benefits and risks of adherence to medical therapy. J. Sci. Pract. Integr.20213110.35122/001c.21386
     [Google Scholar]
  65. LimaS. GagoM. GarrettC. PereiraM.G. Medication adherence in Alzheimer’s disease: The mediator role of mindfulness.Arch. Gerontol. Geriatr.201667929710.1016/j.archger.2016.06.02127475468
     [Google Scholar]
  66. CampbellN.L. BoustaniM.A. SkopeljaE.N. GaoS. UnverzagtF.W. MurrayM.D. Medication adherence in older adults with cognitive impairment: A systematic evidence-based review.Am. J. Geriatr. Pharmacother.201210316517710.1016/j.amjopharm.2012.04.00422657941
     [Google Scholar]
  67. El-SaifiN. MoyleW. JonesC. TuffahaH. Medication adherence in older patients with dementia: A systematic literature review.J. Pharm. Pract.201831332233410.1177/089719001771052428539102
     [Google Scholar]
  68. PorsteinssonA.P. IsaacsonR.S. KnoxS. SabbaghM.N. RubinoI. Diagnosis of early Alzheimer’s disease: Clinical practice in 2021.J. Prev. Alzheimers Dis.20218337138634101796
     [Google Scholar]
  69. BhujbalS.S. KadM.M. PatoleV.C. Recent diagnostic techniques for the detection of Alzheimer’s disease: A short review.Ir. J. Med. Sci.202319252417242610.1007/s11845‑022‑03244‑y36525239
     [Google Scholar]
  70. SmallG.W. RabinsP.V. BarryP.P. BuckholtzN.S. DeKoskyS.T. FerrisS.H. FinkelS.I. GwytherL.P. KhachaturianZ.S. LebowitzB.D. McRaeT.D. MorrisJ.C. OakleyF. SchneiderL.S. StreimJ.E. SunderlandT. TeriL.A. TuneL.E. Diagnosis and treatment of Alzheimer disease and related disorders.JAMA1997278161363137110.1001/jama.1997.035501600830439343469
     [Google Scholar]
  71. LiuC.C. KanekiyoT. XuH. BuG. Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy.Nat. Rev. Neurol.20139210611810.1038/nrneurol.2012.26323296339
     [Google Scholar]
  72. NiaziS.K. MagoolaM. MariamZ. Innovative therapeutic strategies in Alzheimer’s disease: A synergistic approach to neurodegenerative disorders.Pharmaceuticals202417674110.3390/ph1706074138931409
     [Google Scholar]
  73. CaoJ. HouJ. PingJ. CaiD. Advances in developing novel therapeutic strategies for Alzheimer’s disease.Mol. Neurodegener.20181316410.1186/s13024‑018‑0299‑830541602
     [Google Scholar]
  74. LinP. SunJ. ChengQ. YangY. CordatoD. GaoJ. The development of pharmacological therapies for Alzheimer’s disease.Neurol. Ther.202110260962610.1007/s40120‑021‑00282‑z34532845
     [Google Scholar]
  75. YuT.W. LaneH.Y. LinC.H. Novel therapeutic approaches for Alzheimer’s disease: An updated review.Int. J. Mol. Sci.20212215820810.3390/ijms2215820834360973
     [Google Scholar]
  76. GoldeT.E. Disease-modifying therapies for Alzheimer’s disease: More questions than answers.Neurotherapeutics202219120922710.1007/s13311‑022‑01201‑235229269
     [Google Scholar]
  77. CummingsJ. RitterA. ZhongK. Clinical trials for disease-modifying therapies in Alzheimer’s disease: A primer, lessons learned, and a blueprint for the future.J. Alzheimers Dis.201864s1S3S2210.3233/JAD‑17990129562511
     [Google Scholar]
  78. SallowayS. MintzerJ. WeinerM.F. CummingsJ.L. Disease-modifying therapies in Alzheimer’s disease.Alzheimers Dement.2008426579
     [Google Scholar]
  79. ReardonS. FDA approves Alzheimer’s drug lecanemab amid safety concerns.Nature2023613794322722810.1038/d41586‑023‑00030‑336627422
     [Google Scholar]
  80. CummingsJ. New approaches to symptomatic treatments for Alzheimer’s disease.Mol. Neurodegener.20211611-13
     [Google Scholar]
  81. PrinsN.D. ScheltensP. Treating Alzheimer’s disease with monoclonal antibodies: Current status and outlook for the future.Alzheimers Res. Ther.2013565610.1186/alzrt22024216217
     [Google Scholar]
  82. RabinoviciG.D. La JoieR. Amyloid-targeting monoclonal antibodies for Alzheimer disease.JAMA2023330650750910.1001/jama.2023.1170337459124
     [Google Scholar]
  83. SongC. ShiJ. ZhangP. ZhangY. XuJ. ZhaoL. ZhangR. WangH. ChenH. Immunotherapy for Alzheimer’s disease: Targeting β-amyloid and beyond.Transl. Neurodegener.20221111810.1186/s40035‑022‑00292‑335300725
     [Google Scholar]
  84. JuckerM. WalkerL.C. Alzheimer’s disease: From immunotherapy to immunoprevention.Cell2023186204260427010.1016/j.cell.2023.08.02137729908
     [Google Scholar]
  85. MorganD. Immunotherapy for Alzheimer’s disease.J. Intern. Med.20112691546310.1111/j.1365‑2796.2010.02315.x21158978
     [Google Scholar]
  86. SchreinerT.G. CroitoruC.G. HodorogD.N. CuciureanuD.I. Passive anti-amyloid beta immunotherapies in Alzheimer’s disease: From mechanisms to therapeutic impact.Biomedicines2024125109610.3390/biomedicines1205109638791059
     [Google Scholar]
  87. HellerG.T. AprileF.A. MichaelsT.C.T. LimbockerR. PerniM. RuggeriF.S. ManniniB. LöhrT. BonomiM. CamilloniC. De SimoneA. FelliI.C. PierattelliR. KnowlesT.P.J. DobsonC.M. VendruscoloM. Small-molecule sequestration of amyloid-β as a drug discovery strategy for Alzheimer’s disease.Sci. Adv.2020645eabb592410.1126/sciadv.abb592433148639
     [Google Scholar]
  88. Simões-PiresC. ZwickV. NurissoA. SchenkerE. CarruptP.A. CuendetM. HDAC6 as a target for neurodegenerative diseases: What makes it different from the other HDACs?Mol. Neurodegener.201381710.1186/1750‑1326‑8‑723356410
     [Google Scholar]
  89. WalshS. MerrickR. RichardE. NurockS. BrayneC. Lecanemab for Alzheimer’s disease.BMJ2022379o301010.1136/bmj.o301036535691
     [Google Scholar]
  90. Arjmandi-RadS. Vestergaard NielandJ.D. GoozeeK.G. VaseghiS. The effects of different acetylcholinesterase inhibitors on EEG patterns in patients with Alzheimer’s disease: A systematic review.Neurol. Sci.202445241743010.1007/s10072‑023‑07114‑y37843690
     [Google Scholar]
  91. LaiR. HarringtonC. WischikC. Absence of a role for phosphorylation in the tau pathology of Alzheimer’s disease.Biomolecules2016621910.3390/biom602001927070645
     [Google Scholar]
  92. PratiF. BottegoniG. BolognesiM.L. CavalliA. BACE-1 inhibitors: From recent single-target molecules to multitarget compounds for Alzheimer’s disease.J. Med. Chem.201861361963710.1021/acs.jmedchem.7b0039328749667
     [Google Scholar]
  93. MintunM.A. LoA.C. Duggan EvansC. WesselsA.M. ArdayfioP.A. AndersenS.W. ShcherbininS. SparksJ. SimsJ.R. BrysM. ApostolovaL.G. SallowayS.P. SkovronskyD.M. Donanemab in early Alzheimer’s disease.N. Engl. J. Med.2021384181691170410.1056/NEJMoa210070833720637
     [Google Scholar]
  94. EganM.F. KostJ. VossT. MukaiY. AisenP.S. CummingsJ.L. TariotP.N. VellasB. van DyckC.H. BoadaM. ZhangY. LiW. FurtekC. MahoneyE. Harper MozleyL. MoY. SurC. MichelsonD. Randomized trial of verubecestat for prodromal Alzheimer’s disease.N. Engl. J. Med.2019380151408142010.1056/NEJMoa181284030970186
     [Google Scholar]
  95. SevignyJ. ChiaoP. BussièreT. WeinrebP.H. WilliamsL. MaierM. DunstanR. SallowayS. ChenT. LingY. O’GormanJ. QianF. ArastuM. LiM. ChollateS. BrennanM.S. Quintero-MonzonO. ScannevinR.H. ArnoldH.M. EngberT. RhodesK. FerreroJ. HangY. MikulskisA. GrimmJ. HockC. NitschR.M. SandrockA. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease.Nature20165377618505610.1038/nature1932327582220
     [Google Scholar]
  96. HenleyD. RaghavanN. SperlingR. AisenP. RamanR. RomanoG. Preliminary results of a trial of atabecestat in preclinical Alzheimer’s disease.N. Engl. J. Med.2019380151483148510.1056/NEJMc181343530970197
     [Google Scholar]
  97. StoneJ. JohnstoneD.M. MitrofanisJ. O’RourkeM. The mechanical cause of age-related dementia (Alzheimer’s disease): The brain is destroyed by the pulse.J. Alzheimers Dis.201544235537310.3233/JAD‑14188425318547
     [Google Scholar]
  98. OstrowitzkiS. LasserR.A. DorflingerE. ScheltensP. BarkhofF. NikolchevaT. AshfordE. RetoutS. HofmannC. DelmarP. KleinG. AndjelkovicM. DuboisB. BoadaM. BlennowK. SantarelliL. FontouraP. SCarlet RoAD Investigators A phase III randomized trial of gantenerumab in prodromal Alzheimer’s disease.Alzheimers Res. Ther.2017919510.1186/s13195‑017‑0318‑y29221491
     [Google Scholar]
  99. NovakP. ZilkaN. ZilkovaM. KovacechB. SkrabanaR. OndrusM. FialovaL. KontsekovaE. OttoM. NovakM. AADvac1, an active immunotherapy for Alzheimer’s disease and non Alzheimer Tauopathies: An overview of preclinical and clinical development.J. Prev. Alzheimers Dis.201961636930569088
     [Google Scholar]
  100. NovakP. SchmidtR. KontsekovaE. ZilkaN. KovacechB. SkrabanaR. Vince-KazmerovaZ. KatinaS. FialovaL. PrcinaM. ParrakV. Dal-BiancoP. BrunnerM. StaffenW. RainerM. OndrusM. RopeleS. SmisekM. SivakR. WinbladB. NovakM. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer’s disease: A randomised, double-blind, placebo-controlled, phase 1 trial.Lancet Neurol.201716212313410.1016/S1474‑4422(16)30331‑327955995
     [Google Scholar]
  101. BreitnerJ.C. BakerL.D. MontineT.J. MeinertC.L. LyketsosC.G. AsheK.H. BrandtJ. CraftS. EvansD.E. GreenR.C. IsmailM.S. MartinB.K. MullanM.J. SabbaghM. TariotP.N. ADAPT Research Group Extended results of the Alzheimer’s disease anti-inflammatory prevention trial.Alzheimers Dement.20117440241110.1016/j.jalz.2010.12.01421784351
     [Google Scholar]
  102. ScharfS. ManderA. UgoniA. VajdaF. ChristophidisN. A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer’s disease.Neurology199953119720110.1212/WNL.53.1.19710408559
     [Google Scholar]
  103. CalsolaroV. EdisonP. Neuroinflammation in Alzheimer’s disease: Current evidence and future directions.Alzheimers Dement.201612671973210.1016/j.jalz.2016.02.01027179961
     [Google Scholar]
  104. DuboisB. HermineO. Masitinib in mild to moderate Alzheimer’s disease: Results from study AB09004.Alzheimers Dement.202117S9e04986610.1002/alz.049866
     [Google Scholar]
  105. KhezriM.R. Ghasemnejad-BerenjiM. Icariin: A potential neuroprotective agent in Alzheimer’s disease and Parkinson’s disease.Neurochem. Res.202247102954296210.1007/s11064‑022‑03667‑035802286
     [Google Scholar]
  106. JivajeK. InamdarA. GhargeS. KagwadP. SuryawanshiS.S. BhandurgeP. PalledM.S. JaptiV. A brief review on evaluation and exploration of antioxidant activity of mango ginger.Int J Ayurvedic Med202213232132710.47552/ijam.v13i2.1946
     [Google Scholar]
  107. ShalB. DingW. AliH. KimY.S. KhanS. Anti-neuroinflammatory potential of natural products in attenuation of Alzheimer’s disease.Front. Pharmacol.20189MAY54810.3389/fphar.2018.0054829896105
     [Google Scholar]
  108. HalagaliP. InamdarA. SinghJ. AnandA. SadhuP. PathakR. SharmaH. BiswasD. Phytochemicals, herbal extracts, and dietary supplements for metabolic disease management.Endocr. Metab. Immune Disord. Drug Targets202438676520
     [Google Scholar]
  109. NagaharaA.H. TuszynskiM.H. Potential therapeutic uses of BDNF in neurological and psychiatric disorders.Nat. Rev. Drug Discov.201110320921910.1038/nrd336621358740
     [Google Scholar]
  110. TuszynskiM.H. YangJ.H. BarbaD. UH.S. BakayR.A.E. PayM.M. MasliahE. ConnerJ.M. KobalkaP. RoyS. NagaharaA.H. Nerve growth factor gene therapy activation of neuronal responses in Alzheimer disease.JAMA Neurol.201572101139114710.1001/jamaneurol.2015.180726302439
     [Google Scholar]
  111. GalaskoD.R. PeskindE. ClarkC.M. QuinnJ.F. RingmanJ.M. JichaG.A. CotmanC. CottrellB. MontineT.J. ThomasR.G. AisenP. Alzheimer’s Disease Cooperative Study Alzheimer’s Disease Cooperative Study Antioxidants for Alzheimer disease: A randomized clinical trial with cerebrospinal fluid biomarker measures.Arch. Neurol.201269783684110.1001/archneurol.2012.8522431837
     [Google Scholar]
  112. ReisbergB. DoodyR. StöfflerA. SchmittF. FerrisS. MöbiusH.J. Memantine Study Group Memantine in moderate-to-severe Alzheimer’s disease.N. Engl. J. Med.2003348141333134110.1056/NEJMoa01312812672860
     [Google Scholar]
  113. NguyenT.T. NguyenT.T.D. NguyenT.K.O. VoT.K. VoV.G. Advances in developing therapeutic strategies for Alzheimer’s disease.Biomed. Pharmacother.202113911162310.1016/j.biopha.2021.11162333915504
     [Google Scholar]
  114. NunesD. LoureiroJ.A. PereiraM.C. Drug delivery systems as a strategy to improve the efficacy of FDA-approved Alzheimer’s drugs.Pharmaceutics20221411229610.3390/pharmaceutics1411229636365114
     [Google Scholar]
  115. ChaparroC.I.P. SimõesB.T. BorgesJ.P. CastanhoM.A.R.B. SoaresP.I.P. NevesV. A promising approach: Magnetic nanosystems for Alzheimer’s disease theranostics.Pharmaceutics2023159231610.3390/pharmaceutics1509231637765284
     [Google Scholar]
  116. BoyeteyM.J.B. ChoiY. LeeH.Y. ChoiJ. Nanotechnology-based delivery of therapeutics through the intranasal pathway and the blood-brain barrier for Alzheimer’s disease treatment.Biomater. Sci.20241282007201810.1039/D3BM02003G38456516
     [Google Scholar]
  117. LiuN. RuanJ. LiH. FuJ. Nanoparticles loaded with natural medicines for the treatment of Alzheimer’s disease.Front. Neurosci.202317111243510.3389/fnins.2023.111243537877008
     [Google Scholar]
  118. SinghA. MaheshwariS. YadavJ.P. VarshneyA.P. SinghS. PrajapatiB.G. A review on tau targeting biomimetics nano formulations: Novel approach for targeting Alzheimer’s diseases.Cent. Nerv. Syst. Agents Med. Chem.202424329430310.2174/011871524928912024032106593638646682
     [Google Scholar]
  119. SharmaH. AnandA. HalagaliP. InamdarA. PathakR. Advancement of nanoengineered flavonoids for chronic metabolic diseases. In Role of Flavonoids in Chronic Metabolic DiseasesWiley202445951010.1002/9781394238071.ch13
     [Google Scholar]
  120. RossC. TaylorM. FullwoodN. AllsopD. Liposome delivery systems for the treatment of Alzheimer’s disease.Int. J. Nanomedicine2018138507852210.2147/IJN.S18311730587974
     [Google Scholar]
  121. MaitiP. DunbarG. Use of curcumin, a natural polyphenol for targeting molecular pathways in treating age-related neurodegenerative diseases.Int. J. Mol. Sci.2018196163710.3390/ijms1906163729857538
     [Google Scholar]
  122. HebbarS. PoonjaM. ShettyA. DubeyA. In vitro investigation of conventional, chitosan coated and electrosteric stealth liposomes of rivastigmine tartrate for the treatment of Alzheimer’s disease.Int. J. Pharm. Investig.202010455355810.5530/ijpi.2020.4.96
     [Google Scholar]
  123. LuY. GuoZ. ZhangY. LiC. ZhangY. GuoQ. ChenQ. ChenX. HeX. LiuL. RuanC. SunT. JiB. LuW. JiangC. Microenvironment remodeling micelles for Alzheimer’s disease therapy by early modulation of activated microglia.Adv. Sci. (Weinh.)201964180158610.1002/advs.20180158630828531
     [Google Scholar]
  124. RenJ. JiangF. WangM. HuH. ZhangB. ChenL. DaiF. Increased cross-linking micelle retention in the brain of Alzheimer’s disease mice by elevated asparagine endopeptidase protease responsive aggregation.Biomater. Sci.20208236533654410.1039/D0BM01439G33111725
     [Google Scholar]
  125. DuanL. LiX. JiR. HaoZ. KongM. WenX. GuanF. MaS. Nanoparticle-based drug delivery systems: An inspiring therapeutic strategy for neurodegenerative diseases.Polymers2023159219610.3390/polym1509219637177342
     [Google Scholar]
  126. Yavarpour-BaliH. Ghasemi-KasmanM. PirzadehM. Curcumin-loaded nanoparticles: A novel therapeutic strategy in treatment of central nervous system disorders.Int. J. Nanomedicine2019144449446010.2147/IJN.S20833231417253
     [Google Scholar]
  127. DuboisB. López-ArrietaJ. LipschitzS. Masitinib for mild-to-moderate Alzheimer’s disease: Results from a randomized, placebo-controlled, phase 3, clinical trial.Alzheimers Res. Ther.202315139
     [Google Scholar]
  128. DahmaneE.M. RhaziM. TaourirteM. Chitosan nanoparticles as a new delivery system for the anti-HIV drug zidovudine.Bull. Korean Chem. Soc.20133451333133810.5012/bkcs.2013.34.5.1333
     [Google Scholar]
  129. PinheiroR.G.R. GranjaA. LoureiroJ.A. PereiraM.C. PinheiroM. NevesA.R. ReisS. RVG29-functionalized lipid nanoparticles for Quercetin brain delivery and Alzheimer’s disease.Pharm. Res.202037713910.1007/s11095‑020‑02865‑132661727
     [Google Scholar]
  130. DunnB. SteinP. CavazzoniP. Approval of aducanumab for Alzheimer disease-the FDA’s perspective.JAMA Intern. Med.2021181101276127810.1001/jamainternmed.2021.460734254984
     [Google Scholar]
  131. SimsJ.R. ZimmerJ.A. EvansC.D. LuM. ArdayfioP. SparksJ. WesselsA.M. ShcherbininS. WangH. Monkul NeryE.S. CollinsE.C. SolomonP. SallowayS. ApostolovaL.G. HanssonO. RitchieC. BrooksD.A. MintunM. SkovronskyD.M. AbreuR. AgarwalP. AggarwalP. AgroninM. AllenA. AltamiranoD. AlvaG. AndersenJ. AndersonA. AndersonD. ArnoldJ. AsadaT. AsoY. AtitV. AyalaR. BadruddojaM. Badzio-jagielloH. BajacekM. BartonD. BearD. BenjaminS. BergeronR. BhatiaP. BlackS. BlockA. BolouriM. BondW. BouthillierJ. BrangmanS. BrewB. BrisbinS. BriskenT. BrodtmannA. BrodyM. BroschJ. BrownC. BrownstoneP. BukowczanS. BurnsJ. CabreraA. CapoteH. CarrascoA. Cevallos YepezJ. ChavezE. ChertkowH. Chyrchel-paszkiewiczU. CiabarraA. ClemmonsE. CohenD. CohenR. CohenI. ConchaM. CostellB. CrimminsD. Cruz-paganY. CueliA. CupeloR. CzarneckiM. DarbyD. DautzenbergP. De DeynP. De La GandaraJ. DeckK. DibenedettoD. DibuonoM. DinnersteinE. DiricanA. DixitS. DobryniewskiJ. DrakeR. DrysdaleP. DuaraR. DuffyJ. EllenbogenA. FaradjiV. FeinbergM. FeldmanR. FishmanS. FlitmanS. ForchettiC. FragaI. FrankA. FrishbergB. FujigasakiH. FukaseH. FumeroI. FurihataK. GallowayC. GandhiR. GeorgeK. GermainM. GitelmanD. GoetschN. GoldfarbD. GoldsteinM. GoldstickL. Gonzalez RojasY. GoodmanI. GreeleyD. GriffinC. GrigsbyE. GroszD. HafnerK. HartD. HeneinS. HerskowitzB. HigashiS. HigashiY. HoG. HodgsonJ. HohenbergM. HollenbeckL. HolubR. HoriT. HortJ. IlkowskiJ. IngramK.J. IsaacM. IshikawaM. JanuL. JohnstonM. JulioW. JustizW. KagaT. KakigiT. KalaferM. KamijoM. KaplanJ. KarathanosM. KatayamaS. KaulS. KeeganA. KerwinD. KhanU. KhanA. KimuraN. KirkG. KlodowskaG. KowaH. KutzC. KwentusJ. LaiR. LallA. LawrenceM. LeeE. LeonR. LinkerG. LisewskiP. LissJ. LiuC. LoskS. LukaszykE. LynchJ. MacfarlaneS. MacsweeneyJ. ManneringN. MarkovicO. MarksD. MasdeuJ. MatsuiY. MatsuishiK. McallisterP. McconneheyB. McelveenA. McgillL. MeccaA. MegaM. MensahJ. MickielewiczA. MinaeianA. MocherlaB. MurphyC. MurphyP. NagashimaH. NairA. NairM. NardandreaJ. NashM. NasreddineZ. NishidaY. NortonJ. NunezL. OchiaiJ. OhkuboT. OkamuraY. OkorieE. OliveraE. O’mahonyJ. OmidvarO. Ortiz-CruzD. OsowaA. PapkaM. ParkerA. PatelP. PatelA. PatelM. PatryC. PeckhamE. PfefferM. PietrasA. PlopperM. PorsteinssonA. Poulin RobitailleR. PrinsN. PuenteO. RatajczakM. RheeM. RitterA. RodriguezR. Rodriguez AblesL. RojasJ. RossJ. RoyerP. RubinJ. RussellD. RutgersS.M. RutrickS. SadowskiM. SafirsteinB. SagisakaT. ScharreD. SchneiderL. SchreiberC. SchriftM. SchulzP. SchwartzH. SchwartzbardJ. ScottJ. SelemL. SethiP. ShaS. SharlinK. SharmaS. ShiovitzT. ShiwachR. SladekM. SloanB. SmithA. SolomonP. SorialE. SosaE. StedmanM. SteenS. SteinL. StolyarA. StoukidesJ. SudohS. SuttonJ. SyedJ. SzigetiK. TachibanaH. TakahashiY. TatenoA. TaylorJ.D. TaylorK. TcheremissineO. ThebaudA. TheinS. ThurmanL. ToenjesS. TojiH. TomaM. TranD. TruebaP. TsujimotoM. TurnerR. UchiyamaA. UssorowskaD. VaishnaviS. ValorE. VandersluisJ. VasquezA. VelezJ. VergheseC. Vodickova-borzovaK. WatsonD. WeidmanD. WeismanD. WhiteA. WillinghamK. WinkelI. WinnerP. WinstonJ. WolffA. YagiH. YamamotoH. YathirajS. YoshiyamaY. ZbochM. TRAILBLAZER-ALZ 2 Investigators Donanemab in early symptomatic Alzheimer disease.JAMA2023330651252710.1001/jama.2023.1323937459141
     [Google Scholar]
  132. RogersS.L. FarlowM.R. DoodyR.S. MohsR. FriedhoffL.T. Donepezil Study Group A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease.Neurology199850113614510.1212/WNL.50.1.1369443470
     [Google Scholar]
  133. RöslerM. AnandR. Cicin-SainA. GauthierS. AgidY. Dal-BiancoP. StähelinH.B. HartmanR. GharabawiM. BayerT. Efficacy and safety of rivastigmine in patients with Alzheimer’s disease: International randomised controlled trial commentary: Another piece of the Alzheimer’s Jigsaw.BMJ1999318718463364010.1136/bmj.318.7184.63310066203
     [Google Scholar]
  134. RaskindM.A. PeskindE.R. WesselT. YuanW. Galantamine in AD.Neurology200054122261226810.1212/WNL.54.12.226110881250
     [Google Scholar]
  135. HowardR. ZubkoO. BradleyR. HarperE. PankL. O’BrienJ. FoxC. TabetN. LivingstonG. BenthamP. McShaneR. BurnsA. RitchieC. ReevesS. LovestoneS. BallardC. NobleW. NilforooshanR. WilcockG. GrayR. Minocycline in Alzheimer Disease Efficacy (MADE) Trialist Group Minocycline at 2 different dosages vs placebo for patients with mild Alzheimer disease.JAMA Neurol.202077216417410.1001/jamaneurol.2019.376231738372
     [Google Scholar]
  136. QuinnJ.F. RamanR. ThomasR.G. Yurko-MauroK. NelsonE.B. Van DyckC. GalvinJ.E. EmondJ. JackC.R.Jr WeinerM. ShintoL. AisenP.S. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: A randomized trial.JAMA2010304171903191110.1001/jama.2010.151021045096
     [Google Scholar]
  137. SinghA. AnsariV.A. MahmoodT. AhsanF. WasimR. Dendrimers: A neuroprotective lead in Alzheimer disease: A review on its synthetic approach and applications.Drug Res. (Stuttg.)202272841742310.1055/a‑1886‑320835931069
     [Google Scholar]
  138. VohraM. AmirM. SharmaA. WadhwaS. Formulation strategies for nose-to-brain drug delivery.J Pharm Technol Res Manag20221018710210.15415/jptrm.2022.101008
     [Google Scholar]
  139. CraftS. BakerL.D. MontineT.J. MinoshimaS. WatsonG.S. ClaxtonA. ArbuckleM. CallaghanM. TsaiE. PlymateS.R. GreenP.S. LeverenzJ. CrossD. GertonB. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: A pilot clinical trial.Arch. Neurol.2012691293810.1001/archneurol.2011.23321911655
     [Google Scholar]
  140. HansonL.R. FineJ.M. RennerD.B. SvitakA.L. BurnsR.B. NguyenT.M. TuttleN.J. MartiD.L. PanterS.S. FreyW.H.II Intranasal delivery of deferoxamine reduces spatial memory loss in APP/PS1 mice.Drug Deliv. Transl. Res.20122316016810.1007/s13346‑011‑0050‑225786865
     [Google Scholar]
  141. OomsF. WeberP. CarruptP.A. TestaB. A simple model to predict blood-brain barrier permeation from 3D molecular fields.Biochim. Biophys. Acta Mol. Basis Dis.200215872-311812510.1016/S0925‑4439(02)00074‑112084453
     [Google Scholar]
  142. OsmaniR.A. Functionalized polysaccharides based hydrogels: Application in tissue engineering and regenerative medicines.Int. J. Nat. Sci.20235409554107
     [Google Scholar]
  143. JordãoJ.F. Ayala-GrossoC.A. MarkhamK. HuangY. ChopraR. McLaurinJ. HynynenK. AubertI. Antibodies targeted to the brain with image-guided focused ultrasound reduces amyloid-β plaque load in the TgCRND8 mouse model of Alzheimer’s disease.PLoS One201055e1054910.1371/journal.pone.001054920485502
     [Google Scholar]
  144. YuY.J. ZhangY. KenrickM. HoyteK. LukW. LuY. AtwalJ. ElliottJ.M. PrabhuS. WattsR.J. DennisM.S. Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target.Sci. Transl. Med.201138484ra4410.1126/scitranslmed.300223021613623
     [Google Scholar]
  145. GhoraiS.M. DeepA. MagooD. GuptaC. GuptaN. Cell-penetrating and targeted peptides delivery systems as potential pharmaceutical carriers for enhanced delivery across the blood-brain barrier (BBB).Pharmaceutics2023157199910.3390/pharmaceutics1507199937514185
     [Google Scholar]
  146. MillerD.S. Regulation of P-glycoprotein and other ABC drug transporters at the blood-brain barrier.Trends Pharmacol. Sci.201031624625410.1016/j.tips.2010.03.00320417575
     [Google Scholar]
  147. HawkesC.A. McLaurinJ. Clinical immunotherapy trials in Alzheimer’s disease.Drug Discov. Today Ther. Strateg.20085317718310.1016/j.ddstr.2008.09.004
     [Google Scholar]
  148. RyanK.A. WeldonA. HubyN.M. PersadC. BhaumikA.K. HeidebrinkJ.L. BarbasN. StaffendN. FrantiL. GiordaniB. Caregiver support service needs for patients with mild cognitive impairment and Alzheimer disease.Alzheimer Dis. Assoc. Disord.201024217117610.1097/WAD.0b013e3181aba90d19571729
     [Google Scholar]
  149. GilletJ.P. MacadangdangB. FathkeR.L. GottesmanM.M. Kimchi-SarfatyC. The development of gene therapy: From monogenic recessive disorders to complex diseases such as cancer.Methods Mol. Biol.200954255410.1007/978‑1‑59745‑561‑9_119565894
     [Google Scholar]
  150. Cavazzana-CalvoM Hacein-BeyS De Saint BasileG Gene therapy of human severe combined immunodeficiency (SCID)-X1 diseaseScience 20002885466669672
     [Google Scholar]
  151. Förster A FraserP CohenJI LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science20033025644415419
     [Google Scholar]
  152. DavéU.P. AkagiK. TripathiR. ClevelandS.M. ThompsonM.A. YiM. StephensR. DowningJ.R. JenkinsN.A. CopelandN.G. Murine leukemias with retroviral insertions at Lmo2 are predictive of the leukemias induced in SCID-X1 patients following retroviral gene therapy.PLoS Genet.200955e100049110.1371/journal.pgen.100049119461887
     [Google Scholar]
  153. HoweS.J. MansourM.R. SchwarzwaelderK. BartholomaeC. HubankM. KempskiH. BrugmanM.H. Pike-OverzetK. ChattersS.J. de RidderD. GilmourK.C. AdamsS. ThornhillS.I. ParsleyK.L. StaalF.J.T. GaleR.E. LinchD.C. BayfordJ. BrownL. QuayeM. KinnonC. AncliffP. WebbD.K. SchmidtM. von KalleC. GasparH.B. ThrasherA.J. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients.J. Clin. Invest.200811893143315010.1172/JCI3579818688286
     [Google Scholar]
  154. DeakinC.T. AlexanderI.E. KerridgeI. Accepting risk in clinical research: Is the gene therapy field becoming too risk-averse?Mol. Ther.200917111842184810.1038/mt.2009.22319773741
     [Google Scholar]
  155. MorganRA DudleyME WunderlichJR Cancer regression in patients after transfer of genetically engineered lymphocytes.Science 2006314579612612910.1126/science.1129003
     [Google Scholar]
  156. OttM.G. SchmidtM. SchwarzwaelderK. SteinS. SilerU. KoehlU. GlimmH. KühlckeK. SchilzA. KunkelH. NaundorfS. BrinkmannA. DeichmannA. FischerM. BallC. PilzI. DunbarC. DuY. JenkinsN.A. CopelandN.G. LüthiU. HassanM. ThrasherA.J. HoelzerD. von KalleC. SegerR. GrezM. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1.Nat. Med.200612440140910.1038/nm139316582916
     [Google Scholar]
  157. LiuT-C. KirnD. Gene therapy progress and prospects cancer: Oncolytic viruses.Gene Ther.2008151287788410.1038/gt.2008.7218418413
     [Google Scholar]
  158. BankiewiczK.S. ForsayethJ. EberlingJ.L. Sanchez-PernauteR. PivirottoP. BringasJ. HerscovitchP. CarsonR.E. EckelmanW. ReutterB. CunninghamJ. Long-term clinical improvement in MPTP-lesioned primates after gene therapy with AAV-hAADC.Mol. Ther.200614456457010.1016/j.ymthe.2006.05.00516829205
     [Google Scholar]
  159. BjörklundT. KirikD. Scientific rationale for the development of gene therapy strategies for Parkinson’s disease.Biochim. Biophys. Acta Mol. Basis Dis.20091792770371310.1016/j.bbadis.2009.02.00919254760
     [Google Scholar]
  160. IshinoY. ShinagawaH. MakinoK. AmemuraM. NakataA. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product.J. Bacteriol.1987169125429543310.1128/jb.169.12.5429‑5433.19873316184
     [Google Scholar]
  161. MirA. EdrakiA. LeeJ. SontheimerE.J. Type II-C CRISPR-Cas9 biology, mechanism, and application.ACS Chem. Biol.201813235736510.1021/acschembio.7b0085529202216
     [Google Scholar]
  162. LiT. YangY. QiH. CuiW. ZhangL. FuX. HeX. LiuM. LiP. YuT. CRISPR/Cas9 therapeutics: Progress and prospects.Signal Transduct. Target. Ther.2023813610.1038/s41392‑023‑01309‑736646687
     [Google Scholar]
  163. BhardwajS. KesariK.K. RachamallaM. ManiS. AshrafG.M. JhaS.K. KumarP. AmbastaR.K. DurejaH. DevkotaH.P. GuptaG. ChellappanD.K. SinghS.K. DuaK. RuokolainenJ. KamalM.A. OjhaS. JhaN.K. CRISPR/Cas9 gene editing: New hope for Alzheimer’s disease therapeutics.J. Adv. Res.20224020722110.1016/j.jare.2021.07.00136100328
     [Google Scholar]
  164. CaoZ. KongF. DingJ. ChenC. HeF. DengW. Promoting Alzheimer’s disease research and therapy with stem cell technology.Stem Cell Res. Ther.202415113610.1186/s13287‑024‑03737‑w38715083
     [Google Scholar]
  165. BerkowitzC.L. MosconiL. ScheyerO. RahmanA. HristovH. IsaacsonR.S. Precision medicine for Alzheimer’s disease prevention.Healthcare2018638210.3390/healthcare603008230011822
     [Google Scholar]
  166. AntmanE.M. LoscalzoJ. Precision medicine in cardiology.Nat. Rev. Cardiol.2016131059160210.1038/nrcardio.2016.10127356875
     [Google Scholar]
  167. ShinSH BodeAM DongZ Precision medicine: The foundation of future cancer therapeutics.npj Precis Oncol20171112
     [Google Scholar]
  168. RidgePG EbbertM HoytK Assessment of the genetic variance of late-onset Alzheimer’s disease.Neurobiol Aging20164120013200
     [Google Scholar]
  169. BufillE. Ribosa-NoguéR. BlesaR. The therapeutic potential of epigenetic modifications in Alzheimer’s disease.Alzheimer’s Dis Drug DiscovExon citationsBrisbane (AU)2020151164
     [Google Scholar]
  170. HazzanA.A. DauenhauerJ. FollansbeeP. HazzanJ.O. AllenK. OmobepadeI. Family caregiver quality of life and the care provided to older people living with dementia: Qualitative analyses of caregiver interviews. BMC Geriatr 2022; 22(1): 86.10.1186/s12877‑022‑02787‑0
     [Google Scholar]
  171. RaggiA. TascaD. FerriR. A brief essay on non-pharmacological treatment of Alzheimer’s disease.Rev. Neurosci.201728658759710.1515/revneuro‑2017‑000228422708
     [Google Scholar]
  172. GregoryC. LoughS. StoneV. ErzincliogluS. MartinL. Baron-CohenS. HodgesJ.R. Theory of mind in patients with frontal variant frontotemporal dementia and Alzheimer’s disease: Theoretical and practical implications.Brain2002125475276410.1093/brain/awf07911912109
     [Google Scholar]
  173. HerrmannN. ChauS.A. KircanskiI. LanctôtK.L. Current and emerging drug treatment options for Alzheimer’s disease: A systematic review.Drugs201171152031206510.2165/11595870‑000000000‑0000021985169
     [Google Scholar]
  174. PierceT.W.E.A. Recent progress in reminiscence research.International Perspectives on Reminiscence.Life Review and Life Story Work2018
     [Google Scholar]
  175. BradenB.A. GasparP.M. Implementation of a baby doll therapy protocol for people with dementia: Innovative practice.Dementia201514569670610.1177/147130121456153225432935
     [Google Scholar]
  176. JackC.R.Jr BennettD.A. BlennowK. CarrilloM.C. DunnB. HaeberleinS.B. HoltzmanD.M. JagustW. JessenF. KarlawishJ. LiuE. MolinuevoJ.L. MontineT. PhelpsC. RankinK.P. RoweC.C. ScheltensP. SiemersE. SnyderH.M. SperlingR. ElliottC. MasliahE. RyanL. SilverbergN. Contributors NIA-AA research framework: Toward a biological definition of Alzheimer’s disease.Alzheimers Dement.201814453556210.1016/j.jalz.2018.02.01829653606
     [Google Scholar]
  177. DuboisB. VillainN. FrisoniG.B. RabinoviciG.D. SabbaghM. CappaS. BejaninA. BomboisS. EpelbaumS. TeichmannM. HabertM.O. NordbergA. BlennowK. GalaskoD. SternY. RoweC.C. SallowayS. SchneiderL.S. CummingsJ.L. FeldmanH.H. Clinical diagnosis of Alzheimer’s disease: Recommendations of the International Working Group.Lancet Neurol.202120648449610.1016/S1474‑4422(21)00066‑133933186
     [Google Scholar]
  178. JackC.R.Jr TherneauT.M. LundtE.S. WisteH.J. MielkeM.M. KnopmanD.S. Graff-RadfordJ. LoweV.J. VemuriP. SchwarzC.G. SenjemM.L. GunterJ.L. PetersenR.C. Long-term associations between amyloid positron emission tomography, sex, apolipoprotein E and incident dementia and mortality among individuals without dementia: Hazard ratios and absolute risk.Brain Commun.202242fcac01710.1093/braincomms/fcac01735310829
     [Google Scholar]
  179. BucciM. ChiotisK. NordbergA. Alzheimer’s Disease Neuroimaging Initiative Alzheimer’s disease profiled by fluid and imaging markers: Tau PET best predicts cognitive decline.Mol. Psychiatry202126105888589810.1038/s41380‑021‑01263‑234593971
     [Google Scholar]
  180. ChenY.F. MaX. SundellK. AlakaK. SchuhK. RaskinJ. DeanR.A. Quantile regression to characterize solanezumab effects in Alzheimer’s disease trials.Alzheimers Dement. (N. Y.)20162319219810.1016/j.trci.2016.07.00529067306
     [Google Scholar]
  181. BraakH. BraakE. Neuropathological stageing of Alzheimer-related changes.Acta Neuropathol.199182423925910.1007/BF003088091759558
     [Google Scholar]
  182. MosconiL. Glucose metabolism in normal aging and Alzheimer’s disease: Methodological and physiological considerations for PET studies.Clin. Transl. Imaging20131421723310.1007/s40336‑013‑0026‑y24409422
     [Google Scholar]
  183. De LeonM.J. DeSantiS. ZinkowskiR. MehtaP.D. PraticoD. SegalS. ClarkC. KerkmanD. DeBernardisJ. LiJ. LairL. ReisbergB. TsuiW. RusinekH. MRI and CSF studies in the early diagnosis of Alzheimer’s disease.J. Intern. Med.2004256320522310.1111/j.1365‑2796.2004.01381.x15324364
     [Google Scholar]
  184. JackC.R.Jr DicksonD.W. ParisiJ.E. XuY.C. ChaR.H. O’BrienP.C. EdlandS.D. SmithG.E. BoeveB.F. TangalosE.G. KokmenE. PetersenR.C. Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia.Neurology200258575075710.1212/WNL.58.5.75011889239
     [Google Scholar]
  185. ColliotO. ChételatG. ChupinM. DesgrangesB. MagninB. BenaliH. DuboisB. GarneroL. EustacheF. LehéricyS. Discrimination between Alzheimer disease, mild cognitive impairment, and normal aging by using automated segmentation of the hippocampus.Radiology2008248119420110.1148/radiol.248107087618458242
     [Google Scholar]
  186. BobinskiM. de LeonM.J. WegielJ. DesantiS. ConvitA. Saint LouisL.A. RusinekH. WisniewskiH.M. The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer’s disease.Neuroscience200095372172510.1016/S0306‑4522(99)00476‑510670438
     [Google Scholar]
  187. DuA.T. SchuffN. AmendD. LaaksoM.P. HsuY.Y. JagustW.J. YaffeK. KramerJ.H. ReedB. NormanD. ChuiH.C. WeinerM.W. Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer’s disease.J. Neurol. Neurosurg. Psychiatry200171444144710.1136/jnnp.71.4.44111561025
     [Google Scholar]
  188. PanegyresP.K. RogersJ.M. McCarthyM. CampbellA. WuJ.S. Fluorodeoxyglucose-positron emission tomography in the differential diagnosis of early-onset dementia: A prospective, community-based study.BMC Neurol.2009914110.1186/1471‑2377‑9‑4119674446
     [Google Scholar]
  189. HampelH. FrankR. BroichK. TeipelS.J. KatzR.G. HardyJ. HerholzK. BokdeA.L.W. JessenF. HoesslerY.C. SanhaiW.R. ZetterbergH. WoodcockJ. BlennowK. Biomarkers for Alzheimer’s disease: Academic, industry and regulatory perspectives.Nat. Rev. Drug Discov.20109756057410.1038/nrd311520592748
     [Google Scholar]
  190. MarcusC. MenaE. SubramaniamR.M. Brain PET in the diagnosis of Alzheimer’s disease.Clin. Nucl. Med.20143910e413e42610.1097/RLU.000000000000054725199063
     [Google Scholar]
  191. HenriquesA.D. BenedetA.L. CamargosE.F. Rosa-NetoP. NóbregaO.T. Fluid and imaging biomarkers for Alzheimer’s disease: Where we stand and where to head to.Exp. Gerontol.201810716917710.1016/j.exger.2018.01.00229307736
     [Google Scholar]
  192. LiuX. ChenK. WuT. WeidmanD. LureF. LiJ. Use of multimodality imaging and artificial intelligence for diagnosis and prognosis of early stages of Alzheimer’s disease.Transl. Res.2018194566710.1016/j.trsl.2018.01.00129352978
     [Google Scholar]
  193. JohnsonK.A. FoxN.C. SperlingR.A. KlunkW.E. Brain imaging in Alzheimer disease.Cold Spring Harb. Perspect. Med.201224a00621310.1101/cshperspect.a00621322474610
     [Google Scholar]
  194. BensonD.F. KuhlD.E. HawkinsR.A. PhelpsM.E. CummingsJ.L. TsaiS.Y. The fluorodeoxyglucose 18F scan in Alzheimer’s disease and multi-infarct dementia.Arch. Neurol.1983401271171410.1001/archneur.1983.040501100290036605139
     [Google Scholar]
  195. FosterN.L. ChaseT.N. FedioP. PatronasN.J. BrooksR.A. ChiroG.D. Alzheimer’s disease.Neurology198333896196510.1212/WNL.33.8.9616603596
     [Google Scholar]
  196. FriedlandR.P. BudingerT.F. GanzE. YanoY. MathisC.A. KossB. OberB.A. HuesmanR.H. DerenzoS.E. Regional cerebral metabolic alterations in dementia of the Alzheimer type: Positron emission tomography with [18F]fluorodeoxyglucose.J. Comput. Assist. Tomogr.19837459059810.1097/00004728‑198308000‑000036602819
     [Google Scholar]
  197. SharmaH. ChandraP. PathakR. BhandariM. ArushiS.V. Advancements in the therapeutic approaches to treat neurological disorders.Cah Magellanes-NS.20246243284389
     [Google Scholar]
  198. ChandraP. SharmaH. Phosphodiesterase inhibitors for treatment of Alzheimer’s disease.Indian Drugs202461772210.53879/id.61.07.14382
     [Google Scholar]
  199. PathakR. SharmaS. BhandariM. NogaiL. MishraR. SaxenaA. Reena KmS.H. Neuroinflammation at the crossroads of metabolic and neurodegenerative diseases: Causes, consequences and interventions.J. Exp. Zool. India20242122447246110.59467/jez.2024.27.2.2447
     [Google Scholar]
  200. SharmaH. PathakR. BiswasD. Unveiling the therapeutic potential of modern probiotics in addressing neurodegenerative disorders: A comprehensive exploration, review and future perspectives on intervention strategies.Curr. Psychiatry Res. Rev.20242010.2174/0126660822304321240520075036
     [Google Scholar]
  201. ChandraP. AliZ. FatimaN. SharmaH. SachanN. SharmaK.K. VermaA. Shankhpushpi (Convolvulus pluricaulis): Exploring its cognitive enhancing mechanisms and therapeutic potential in neurodegenerative disorders.Curr. Bioact. Compd.20242010.2174/0115734072292339240416095600
     [Google Scholar]
  202. SharmaH. ChandraP. Effects of natural remedies on memory loss and Alzheimer’s disease.Afr.J.Bio.Sc.20246718721110.33472/AFJBS.6.7.2024.187‑211
     [Google Scholar]
  203. DasS. MukherjeeT. MohantyS. NayakN. MalP. AshiqueS. PalR. MohantoS. SharmaH. Impact of NF-κB signaling and Sirtuin-1 protein for targeted inflammatory intervention.Curr. Pharm. Biotechnol.20242510.2174/011389201030146924040908221238638042
     [Google Scholar]
  204. SharmaH. KaushikM. GoswamiP. SreevaniS. ChakrabortyA. AshiqueS. PalR. Role of miRNAs in brain development.MicroRNA20241329610910.2174/012211536628712724032205451938571343
     [Google Scholar]
  205. AshiqueS. PalR. SharmaH. MishraN. GargA. Unraveling the emerging niche role of extracellular vesicles (EVs) in traumatic brain injury (TBI).CNS Neurol. Disord. Drug Targets202423111357137010.2174/011871527328815524020106504138351688
     [Google Scholar]
  206. SharmaH ChandraP VermaA PandeySN KumarP SighA Therapeutic approaches of nutraceuticals in the prevention of neurological disorders.Eur Chem Bull20231251575 1596
     [Google Scholar]
  207. SharmaH. ChandraP. Challenges and future prospects: A benefaction of phytoconstituents on molecular targets pertaining to Alzheimer’s disease.Int. J. Pharm. Investig.202314111712610.5530/ijpi.14.1.15
     [Google Scholar]
  208. SharmaH. PathakR. KumarN. NogaiL. MishraR. BhandariM. KoliM. PandeyP. Endocannabinoid system: Role in depression, recompense, and pain control.J. Surv. Fish..2023104S2743275110.17762/sfs.v10i4S.1655
     [Google Scholar]
  209. SharmaH. RaniT. KhanS. An insight into neuropathic pain: A systemic and up-to-date review.Int. J. Pharm. Sci. Res.202314260762110.13040/IJPSR.0975‑8232.14(2).607‑21
     [Google Scholar]
  210. Spoorthi ShettyS. HalagaliP. JohnsonA.P. SpandanaK.M.A. GangadharappaH.V. Oral insulin delivery: Barriers, strategies, and formulation approaches: A comprehensive review.Int. J. Biol. Macromol.2023242Pt 312511410.1016/j.ijbiomac.2023.12511437263330
     [Google Scholar]
  211. RaneS AdhyapakA GhargeS KoliR SingadiR HalagaliP UV and HPTLC-based approaches towards rutin determination in abutilon theophrasti extract. J. Pharm. Sci.2022147790794
     [Google Scholar]
  212. HalagaliP. SingadiR. Ranganath ArjunH. RakshanaaG.S. NairS.P. HalagaliP. SomannaP. Role of traditional plant compounds in the treatment of neuropsychiatric diseases.Int. J. Pharm. Investig.2023141485410.5530/ijpi.14.1.7
     [Google Scholar]
  213. JamesA. HalagaliP. JafarM. SanuJ. BharadwajR.K. ShajuB. BasheerS. ArjunH.R. SomannaP. Formulation and evaluation of fumaria parviflora loaded oil in water emulsion-based cream.Int. J. Pharm. Investig.202414249350310.5530/ijpi.14.2.59
     [Google Scholar]
  214. SharmaH. RachamallaH.K. MishraN. ChandraP. PathakR. AshiqueS. Introduction to exosome and its role in brain disorders BT - Exosomes based drug delivery strategies for brain disorders. MishraN. AshiqueS. GargA. ChithravelV. AnandK. SingaporeSpringer Nature Singapore202413510.1007/978‑981‑99‑8373‑5_1
     [Google Scholar]
  215. SharmaH. TyagiS.J. ChandraP. Role of exosomes in Parkinson’s and Alzheimer’s diseases BT - Exosomes based drug delivery strategies for brain disorders. MishraN. AshiqueS. GargA. ChithravelV. AnandK. SingaporeSpringer Nature Singapore202414718210.1007/978‑981‑99‑8373‑5_6
     [Google Scholar]
  216. KumarP. SharmaH. SinghA. PandeyS.N. ChandraP. Correlation between exosomes and neuro-inflammation in various brain disorders bt- Exosomes based drug delivery strategies for brain disorders. MishraN. AshiqueS. GargA. ChithravelV. AnandK. SingaporeSpringer Nature Singapore202427330210.1007/978‑981‑99‑8373‑5_11
     [Google Scholar]
/content/journals/cpd/10.2174/0113816128344571241018154506
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Cutting-edge Strategies for Overcoming Therapeutic Barriers in Alzheimer's Disease
Curr. Pharm. Des. 31, 598 (2025); https://doi.org/10.2174/0113816128344571241018154506
/content/journals/cpd/10.2174/0113816128344571241018154506
/content/journals/cpd/10.2174/0113816128344571241018154506
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  • Article Type:     Review Article
Keyword(s): Alzheimer's disease; biomarkers; blood-brain barrier; drug delivery systems; gene therapy; therapeutic barriers

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